We have previously shown that in the first 3 weeks of life puppies depress their ventilation and do not increase heart rate in response to hypoxia during sleep; subsequently, they do respond to hypoxia by increasing ventilation and heart rate. We have also demonstrated that aborted SIDS infants may hypoventilate in the first 2 months of life during sleep and that their ventilatory pattern approaches that of normal infants at later ages. Since 1) there is indirect evidence that hypoxia plays a role in the pathogenesis of the Sudden Infant Death Syndrome (SIDS), 2) hypoxia depresses ventilation in immature animals and preterm infants, and 3) endorphins are generally held to be inhibitory modulators of cardiorespiratory control mechanisms, we propose to study the role of endorphins in the maturation of ventilatory and cardiovascular function during sleep under normoxic and hypoxic conditions. For this purpose, we will infuse indorphin agonists and antagonists intravenously in puppies and adult dogs during sleep under normoxic and hypoxic conditions. Using techniques already in full operation in our laboratory, we will measure ventilation and ventilatory pattern by the barometric method, heart rate and heart rate variability with a preprocessor, cardiac output using the Fick principle, and O2 consumption in a closed system. Sleep will be staged using electroencephalographic, electrooculographic and behavioral criteria. Using a receptor binding assay, we will also measure the total opiate concentration in the CSF during sleep in normoxic and hypoxic conditions and will correlate this with cardiovascular and ventilatory response to hypoxia. Because there are data to indicate that angiotensin converting enzyme (ACE) is an enkephalinase and because we have previously shown that ACE activity is inhibited by hypoxia, we also propose in-vitro studies of cultured endothelial cells to evaluate the enkephalinase activity of ACE under normoxic and hypoxic conditions and in-vivo studies to test its physiologic importance. Understanding the biochemical basis of hypoventilation, apnea and cardiovascular instability in the very young infant during sleep is essential for the development of new approaches to the treatment of a variety of pediatric illnesses early in life including SIDS and apnea of prematurity.